The aim of this research proposal is to use monoclonal antibodies as molecular probes to define the differences between the surface structures of a spontaneously metastasizing human lung adenocarcinoma (T291) and its metastasizing variant (T291Met) in order to identify those surface characteristics that are critical in metastatic processes. To achieve this aim, hybridomas will be generated to T291 and to T291Met and those monoclonal antibodies will be selected which selectively recognize antigens on either of these cell lines. Such reagents will make it possible 1) to clearly define surface antigenic differences between the parental tumor line and its metastatic variant; 2) to identify the biochemical and immunological nature of the antigens identified; and 3) to evaluate whether the monoclonal antibodies can inhibit the development of metastases. It is anticipated that results from such studies will contribute to a better understanding of the intricate events and surface changes involved in the clonal evolution of sub-populations of tumor cells that are capable of forming metastases.